mTORC2 contributes to murine lupus
biorxiv(2021)
摘要
The development of systemic lupus erythematosus (SLE) is associated with overactivation of the type I interferon (IFN) pathway, lymphopenia, and increased follicular helper T (Tfh) cell differentiation. However, the cellular and molecular mechanisms of action of type I IFN in SLE remains incompletely understood. Here we show that type I IFN activates the mechanistic target of rapamycin complex 2 (mTORC2) in T cells to promote T cell lymphopenia. mTORC2 also promotes Tfh differentiation and disrupts Treg homeostasis. Inactivation of mTORC2 greatly ameliorated the immunopathology in a lupus-prone mouse model, associated with reduced Tfh differentiation, normalization of Treg homeostasis and reduced T cell glucose metabolism. These data indicate that mTORC2 acts downstream of type I IFN and costimulatory receptor ICOS, to promote T cell lymphopenia and Tfh differentiation in murine lupus development, suggesting that inhibition of mTORC2 could limit lupus disease progression.
### Competing Interest Statement
The authors have declared no competing interest.
* Tfh
: follicular helper T cells
Treg
: regulatory T cells
SLE
: systemic lupus erythematosus
mTOR
: mechanistic target of rapamycin
IFN
: interferon
GC
: germinal center
EF
: extrafollicular
Tfr
: follicular regulatory T cells
ICOS
: inducible T-cell costimulatory.
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